Voluntary Exercise Improves Radiation-induced Brain Injury in Mice.

IF 2.7 3区 医学 Q2 BIOLOGY
Hiroyuki Miura, Tomonori Furukawa, Chihiro Sato, Ayaka Monden, Tomohito Nunomura, Kana Umamichi, Kai Hatakenaka, Rina Yamazaki, Masaru Yamaguchi, Shuhei Koeda, Junko Yamada
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Abstract

Radiation-induced brain injury (RBI) adversely affects the quality of life and prognosis of patients with brain tumors who undergo radiation therapy. Although rehabilitation strategies are recommended for mitigating RBI, the underlying mechanisms remain poorly understood. Here, we focused on RBI after fractionated whole-brain irradiation (WBI) in adult mice and examined the effects of voluntary exercise (VE) on cognitive function, growth factors, neurogenesis, and synaptic plasticity. Male C57BL/6J mice, aged 10-12 weeks, were divided into four groups: cham control (Ctl), WBI, Ctl + VE, and WBI + VE. The WBI total dose was 8 Gy (4 Gy × 2 fractions). Voluntary exercise was provided for three weeks using a voluntary running wheel that was accessible 24 h a day. The effects of RBI and VE were analyzed using behavioral, biochemical, immunohistological, and electrophysiological evaluations. WBI significantly impaired cognitive functions including spatial working memory, reference memory, and cognitive flexibility. Additionally, WBI led to reduced plasma mature brain-derived neurotrophic factor (mBDNF) levels, neurogenic differentiation 1 (NeuroD1)-positive cell density in the dentate gyrus, and long-term potentiation in the hippocampal cornu ammonis 1 region. Conversely, VE intervention ameliorated these cognitive deficits and increased mBDNF levels, enhanced NeuroD1-positive cell density, and strengthened long-term potentiation. Our findings suggest that VE intervention mitigates the effects of RBI in adult mice by promoting neurogenesis and enhancing synaptic plasticity via growth factor upregulation. These results underscore the importance of physical activity in rehabilitation and suggest that VE is a noninvasive strategy for improving cognitive function in patients affected by RBI.

自愿运动改善小鼠辐射引起的脑损伤。
放射性脑损伤(RBI)对接受放射治疗的脑肿瘤患者的生活质量和预后有不利影响。虽然康复策略被推荐用于减轻RBI,但其潜在机制仍然知之甚少。在这里,我们重点研究了成年小鼠分块全脑照射(WBI)后的RBI,并研究了自主运动(VE)对认知功能、生长因子、神经发生和突触可塑性的影响。10 ~ 12周龄雄性C57BL/6J小鼠分为4组:对照组(Ctl)、WBI组、Ctl + VE组和WBI + VE组。WBI总剂量为8 Gy (4 Gy × 2次)。自愿运动提供了三个星期,使用自愿跑步轮,每天24小时可访问。采用行为学、生化、免疫组织学和电生理评价分析RBI和VE的效果。脑外伤显著损害认知功能,包括空间工作记忆、参考记忆和认知灵活性。此外,WBI导致血浆成熟脑源性神经营养因子(mBDNF)水平降低,齿状回神经源性分化1 (NeuroD1)阳性细胞密度降低,海马海马角区长时程增强。相反,VE干预改善了这些认知缺陷,增加了mBDNF水平,增强了neurod1阳性细胞密度,并加强了长期增强。我们的研究结果表明,VE干预可以通过提高生长因子来促进神经发生和增强突触可塑性,从而减轻成年小鼠RBI的影响。这些结果强调了身体活动在康复中的重要性,并表明VE是改善RBI患者认知功能的一种无创策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Radiation research
Radiation research 医学-核医学
CiteScore
5.10
自引率
8.80%
发文量
179
审稿时长
1 months
期刊介绍: Radiation Research publishes original articles dealing with radiation effects and related subjects in the areas of physics, chemistry, biology and medicine, including epidemiology and translational research. The term radiation is used in its broadest sense and includes specifically ionizing radiation and ultraviolet, visible and infrared light as well as microwaves, ultrasound and heat. Effects may be physical, chemical or biological. Related subjects include (but are not limited to) dosimetry methods and instrumentation, isotope techniques and studies with chemical agents contributing to the understanding of radiation effects.
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